THE OCCURRENCE OF CARRIERS OF DISEASE-PRO- DUCING TYPES OF PNEUMOCOCCUS.

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1 Published Online: 1 July, 1915 Supp Info: Downloaded from jem.rupress.org on November 21, 2018 THE OCCURRENCE OF CARRIERS OF DISEASE-PRO- DUCING TYPES OF PNEUMOCOCCUS. BY A. R. DOCHEZ, M.D., AND O. T. AVERY, M.D. (From the Hospital of The Rockefeller Institute for Medical Research.) (Received for publication, May 20, 1915.) In previous papers 1 we have discussed the varieties of pneumococcus responsible for the production of lobar pneumonia and the differences that exist between such organisms and those found in the mouths of healthy individuals. The pneumococci obtained from persons suffering from lobar pneumonia have been divided into four groups. We have pointed out that the first three groups are comprised of disease-producing races, and are responsible for about 75 per cent of all cases of lobar pneumonia. Approximately 25 per cent of cases of pneumonia are due to the fourth group. The pneumococci of this group cannot readily be distinguished" from those dwelling in the normal human mouth. Disease caused by the highly parasitic types is usually much more severe than that occasioned by the strains which are indistinguishable from the sputum pneumococci. Inasmuch as the highly virulent forms are always associated with disease, and only occur in the mouths of healthy individuals under the special conditions which are reported in this paper, the evidence is strong that in the spread of lobar pneumonia the disease in a majority of instances is transmitted from one individual to another. Infectious diseases usually spread by immediate contact, through the intermediation of a temporary host, or by the agency of a healthy carrier. The importance of these modes of transmission varies with different diseases and in many instances more than one of these mechanisms may be involved. In all likelihood the healthy carrier may be a greater menace to the health of the community than the 1 Dochez, A. R., and Gillespie, L. J., dour. Am. Med. Assn., 1913, lxi, 727. Dochez, A. R., and Avery, O. T., dour. Exper. Med., 1915, xxi,

2 106 Carriers of Disease-Producing Types of Pneumocoecus. infected individual, largely because of failure to recognize the carrier condition. In the epidemiology of certain diseases, notably typhoid and epidemic cerebrospinal meningitis, the importance of the carrier state is well known because of the definite tracing of loci of disease to such a condition. The more readily a disease is transmitted from one individual to another, the greater becomes the number of instances at any one time, and consequently the more vigorous the search for the source of infection. The sporadic occurrence of lobar pneumonia, combined with the inability to distinguish disease-producing types of pneumococcus from those habitually living in normal mouths, has probably been responsible for the failure to establish a well defined epidemiology for this disease. It is not our purpose in this paper to discuss the importance of immediate contact as a cause of the spread of pneumonia, for, although instances have occurred in which two closely associated individuals, such as husband and wife, have been infected within a short period with the same type of pneumococcus, cases of pneumonia usually develop at such wide intervals of space and time that direct contact relationships are obscured. Inasmuch as fully 75 per cent of all cases of lobar pneumonia are caused by peculiarly distinct races of pneumococci, not occurring in the normal mouth, then, as we have previously assumed, these instances of the disease nmst be due to contact infection, either direct or indirect, and some mechanism must exist by means of which the etiological agent is transmitted from one individual to another. In the present study we shall show that persons closely associated with individuals suffering from pneumonia in a large percentage of instances harbor in their mouths pneumococci of the same type as those causing the disease, that such organisms are not found in the mouths of normal individuals not exposed to pneumonia, and that the considerable period of time during which these organisms are carried may in part account for the sporadic occurrence of individual cases of pneumonia. An additional means of transmission exists in the fact that the recovered case also may carry the pneumococcus responsible for his disease during a relatively long period of time.

3 A. 1~. Dochez and O. T. Avery. 107 In the present paper are presented the studies of the pneumococci obtained from the mouths of persons associated with cases of pneumonia, of the type of pneumococcus encountered in the mouths of normal unexposed individuals, and of the period of time during which convalescents harbor the disease-producing organisms. For TABLE I. Incidence of Carrier Condition in Healthy Individuals in Contact ~4th Lobar Pneumonia. Case I Type ofinfectin~ Relationship of Type found in No. i pneumococcus, associates, associates. ]3uration of period of carrying W B o Husband Nurse Daughter Father Daughter Son Nurse No pneumocoecus No pneumoeoceus No pneumococcus No pneumocoecus f No pneumococeus f Io days + 24 days. Undetermined. Undetermined. Undetermined. 9 days + 27 days+ D~eloped pneumonia, Type Type li Husband Brother Daughter Son Brother-in-law Physician 45 days. No pneumocoecus No pneumococcus No pneumoeoceus 7 days+ No pneumococcus 2i days.

4 108 Carriers of Disease-Producing Types of Pneumocoecus. Summary. TABLE I.--Concluded. ~l'ype of pneumococcus, No. of cases. Positive contacts. Per cent, 8... / I 24 Total... f 32 Approximate duration of carrier state 23 days. 3 IO 13, the sake of clearness, an explanation of our classification of pneumococci is given. The organisms have been placed into four groups, numbered from I to IV. Groups I, II, and III are found only in association with disease and are distinctly parasitic in type. Members of Groups I, II, and III are recognized by their imanune reactions which are identical within the respective group. Group IV consists of a heterogeneous series of strains which are not related antigenically, and which cause a minority of cases of pneumonia, and from which the pneumococcus occurring in the normal mouth is indistinguishable. In the Tables I to IV the pneumococci studied are classified according to this numerical grouping. TABLE II. Type of Pneumococcus Isolated from Sputum of Normal Individuals, Pnetlmococcas. Incidence. Per cent. C. [' ontacts ).[ 8 7.o No pneumococcus 47 4z.6 Total 113 Pneumococcus present Pneumococcus absent TABLE III. Type of Pneumocoeeus Isolated from Individuals with Lobar Pneumonia. ~Paeumococcus. No. of cases, Per cent I Total No. of cases 223

5 A. R. Dochez and O. T. Avery. 109 TABLE IV. Persistence of Disease-Producing Type of Pneumococcus during Convalescence. Type of pneumococcus Type of pneumocoecus Case No. during height of disease, after recovery days,. 65 days, days, streptococcus. 73 days, streptococcus days, days, days, days, days, days, days, days,. 49 days, no pneumococcus days, no pneumococcus days,. W 15 days,. 23 days,. I3 14 days, no pneumococcus io days, days, no pneumococcus days,. 29 days, no pneumococcus days, no pneumococcus days, days, streptococcus. 48 days,. lo8 days, days, days, streptococcus. 40 days, t 47 days, streptococcus. 78 days, days, days,. 25 days,. 182o 30 days, days,. 188o 63 days,. 195o 21 days, days, days, streptococcus days, no pneumococcus days,. 17 days, no pneumococcus.

6 110 Carriers of Disease-Producing Types of Pneumococcus. TABLE IV.--Coucluded. Type of pnemococcus Type of pneumococcus Case No. during height of disease, after recovery days,. 43 days, days, 11o pneumococcus days, days, I5 days, days, io days,. 25 days, no pneumococcus days, days, no pneumococcus I 13 days, I. 73 days, I I6 days, I. 34 days, no pneumococcus I 14 days, I. In the above four tables are given the main facts upon which we base our assumption that in the majority of cases lobar pnemnonia is a disease the continued wide-spread incidence of which is dependent upon communication of infection from one individual to another. Table I establishes beyond doubt the existence of healthy carriers of the disease-producing types of pneumococcus. The study of the carrier state was limited to the investigation of infection with pneumococcus Types I and II because of the relative ease with which these organisms can be distinguished from other types of pneumococcus. Out of a total of thirty-two cases studied, at least one carrier of infection among the patient's associates was found in thirteen insta!aces, 4o.6 per cent. Types I and II show apwoximately the same percentage incidence of the carrier condition, and in every instance the pneumococcus isolated corresponds in type with that of the infected individual. The approximate duration of the carrier state has been twenty-three days, which is probably somewhat shorter than would be found had it been possible to retain under observation all carriers until the disease-producing type of pneumococcus had disappeared from the mouth

7 A. R. Dochez and O. T. Avery. 111 flora. Study of Table I shows that positive carriers are more commonly observed among females than among males, a fact that is probably accounted for by the more frequent service of the former in a nursing capacity, thus entailing more intimate association with the sick. Tables II, III, and IV develop somewhat further, points brought out in a previous communication. In Table II is shown the incidence of pneumococcus in the mouth flora of normal individuals and the classification of such pneumococci. All normal individuals studied are given in this table, whether in contact with cases of lobar pneumonia or not. Pneumococcus was found in 58.4 per cent of all instances and was absent in 41.6 per cent. Of the cases in which pneumococcus has been found, 48.6 per cent of the organisms have been of the sputum type and 9.6 per cent have been of the disease-producing type. All the latter have occurred in individuals intimately associated with cases of lobar pneumonia, and their presence is dependent upon this association. Determination of contact carriers of pneumococci belonging to Group III, Pneumococcus mucosus, presents certain difficulties. Only recently have we been able to obtain an immune serum effective against organisms of this group. Further development of the study of the nmcous group is showing that certain organisms resembling in their cultural reactions Pneumococcus mucosus, are, in reality, mucous types of streptococcus. The latter varieties are frequently found in normal sputum, and have led to some confusion. With the working out of the serological reactions of the true Pneumococcus mucosus, evidence is accumulating that this organism is as strictly pathogenic in type, and has quite as specific immunological characteristics as pneumococci belonging to Groups I and II. For comparison with the statistics given in Table II, which illustrates the prevalence of the mouth type of pneumococcus in normal individuals, Table III is added to show the percentage incidence of the fixed types of pneumococci observed in individuals suffering from lobar pneumonia. In this table the highly pathogenic types are dominant, being responsible for 77.2 per cent of all infections studied. This fact is convincing evidence that specific types of

8 112 Carriers of Disease-Producing Types of Pneumococcus. pneumococci are mainly responsible for the production of lobar pneumonia. The dominance of these organisms in disease is in striking contrast to the high percentage incidence of the sputum type of pneumococcus in the mouth flora of normal individuals. Table IV shows the length of time during which recovered cases of pneumonia harbor the organism responsible for their disease. The period of carrying is measured from the date of onset of the pneumonia. The shortest time in which the disease-producing pneumococcus has disappeared from the mouth has been twelve days, and the longest duration of carrying has been ninety days. These results show that pathogenic types of pneumococcus persist in the mouths of individuals recovering from lobar pneumonia for a variable period of time. Because of wide intervals between observations, the average duration of this condition can only be approximately determined, and has been found to be about twentyeight days. The studies detailed in this paper show that there are two sources of danger in the spread of pneumococcus infection. One lies in the occurrence of healthy carriers of disease-producing pneumococci among individuals associated with cases of pneumonia, and the other in the fact that patients recovering from the disease harbor the responsible organism for a considerable length of time. The actual tracing of cases of pneumonia to examples of the carrier state is difficult, but even the small amount of effort that has so far been devoted to this side of the study has brought to light an occasional suggestive fact. SUMiVIARY. Lobar pneumonia in 75 per cent of instances is due to specific types of pneumococci possessed of a high degree of pathogenicity. Although pneumococci occur in the mouths of 60 per cent of normal individuals, such organisms are readily distinguishable from the highly parasitic types of pneumococcus responsible for the severe forms of lobar pneumonia, a convincing proof that infection in this disease is, in the majority of instances, not autogenic in nature, but is derived from some extraneous source. In a high percentage of instances healthy persons intimately associated with

9 A. R. Dochez and O. T. Avery. 113 cases of lobar pneumonia harbor the disease-producing types of pneumococcus. In every such instance the pneumococcus isolated has corresponded in type with that of the infected individual. Convalescents from pneumonia carry for a considerable length of time the type of pneumococcus with which they have been infected. The existence of the carrier state among healthy persons and among those recently recovered from pneumonia establishes a basis for understanding the mechanism by means of which lobar pneumonia spreads and maintains its high incidence from year to year.